LIRA3_HUMAN
ID LIRA3_HUMAN Reviewed; 439 AA.
AC Q8N6C8; J3KPM2; O15469; O15470; O75016; Q8N151; Q8N154; Q8NHJ1; Q8NHJ2;
AC Q8NHJ3; Q8NHJ4;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Leukocyte immunoglobulin-like receptor subfamily A member 3;
DE AltName: Full=CD85 antigen-like family member E;
DE AltName: Full=Immunoglobulin-like transcript 6;
DE Short=ILT-6;
DE AltName: Full=Leukocyte immunoglobulin-like receptor 4;
DE Short=LIR-4;
DE AltName: Full=Monocyte inhibitory receptor HM43/HM31;
DE AltName: CD_antigen=CD85e;
DE Flags: Precursor;
GN Name=LILRA3; Synonyms=ILT6, LIR4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-3, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Lung, and Monocyte;
RX PubMed=9278324;
RA Arm J.P., Nwankwo C., Austen K.F.;
RT "Molecular identification of a novel family of human Ig superfamily members
RT that possess immunoreceptor tyrosine-based inhibition motifs and homology
RT to the mouse gp49B1 inhibitory receptor.";
RL J. Immunol. 159:2342-2349(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-3, AND TISSUE
RP SPECIFICITY.
RX PubMed=9548455;
RA Borges L., Hsu M.-L., Fanger N., Kubin M., Cosman D.;
RT "A family of human lymphoid and myeloid Ig-like receptors, some of which
RT bind to MHC class I molecules.";
RL J. Immunol. 159:5192-5196(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=9079806; DOI=10.1002/eji.1830270313;
RA Samaridis J., Colonna M.;
RT "Cloning of novel immunoglobulin superfamily receptors expressed on human
RT myeloid and lymphoid cells: structural evidence for new stimulatory and
RT inhibitory pathways.";
RL Eur. J. Immunol. 27:660-665(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-3.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-420, AND VARIANTS ARG-107 AND
RP HIS-301.
RX PubMed=12750859; DOI=10.1007/s00251-003-0561-1;
RA Norman P.J., Carey B.S., Stephens H.A., Vaughan R.W.;
RT "DNA sequence variation and molecular genotyping of natural killer
RT leukocyte immunoglobulin-like receptor, LILRA3.";
RL Immunogenetics 55:165-171(2003).
RN [7]
RP PROTEIN SEQUENCE OF 24-38.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP GLYCOSYLATION AT ASN-140; ASN-281; ASN-302; ASN-341 AND ASN-431, AND
RP FUNCTION.
RX PubMed=24085305; DOI=10.1074/jbc.m113.478578;
RA Lee T.H., Mitchell A., Liu Lau S., An H., Rajeaskariah P., Wasinger V.,
RA Raftery M., Bryant K., Tedla N.;
RT "Glycosylation in a mammalian expression system is critical for the
RT production of functionally active leukocyte immunoglobulin-like receptor A3
RT protein.";
RL J. Biol. Chem. 288:32873-32885(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 24-120, DISULFIDE BOND, AND
RP FUNCTION.
RX PubMed=21559424; DOI=10.1371/journal.pone.0019245;
RA Ryu M., Chen Y., Qi J., Liu J., Fan Z., Nam G., Shi Y., Cheng H., Gao G.F.;
RT "LILRA3 binds both classical and non-classical HLA class I molecules but
RT with reduced affinities compared to LILRB1/LILRB2: structural evidence.";
RL PLoS ONE 6:E19245-E19245(2011).
CC -!- FUNCTION: Acts as soluble receptor for class I MHC antigens. Binds both
CC classical and non-classical HLA class I molecules but with reduced
CC affinities compared to LILRB1 or LILRB2. Binds with high affinity to
CC the surface of monocytes, leading to abolish LPS-induced TNF-alpha
CC production by monocytes. {ECO:0000269|PubMed:21559424,
CC ECO:0000269|PubMed:24085305}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N6C8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N6C8-2; Sequence=VSP_045887;
CC Name=3;
CC IsoId=Q8N6C8-3; Sequence=VSP_045886;
CC -!- TISSUE SPECIFICITY: Detected in B-cells, and at lower levels in natural
CC killer (NK) cells. Detected in peripheral blood monocytes and lung.
CC {ECO:0000269|PubMed:9278324, ECO:0000269|PubMed:9548455}.
CC -!- PTM: N-glycosylation is required for ligand binding.
CC {ECO:0000269|PubMed:24085305}.
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DR EMBL; U91926; AAB68666.1; -; mRNA.
DR EMBL; U91927; AAB68667.1; -; mRNA.
DR EMBL; AF025527; AAB87661.1; -; mRNA.
DR EMBL; AF014924; AAC51886.1; -; mRNA.
DR EMBL; AC008984; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010518; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028208; AAH28208.1; -; mRNA.
DR EMBL; AF482762; AAM18035.1; -; Genomic_DNA.
DR EMBL; AF482763; AAM18036.1; -; Genomic_DNA.
DR EMBL; AF482764; AAM18037.1; -; Genomic_DNA.
DR EMBL; AF482765; AAM18038.1; -; Genomic_DNA.
DR EMBL; AF482766; AAM18039.1; -; Genomic_DNA.
DR EMBL; AF482767; AAM18040.1; -; Genomic_DNA.
DR EMBL; AF482768; AAM18041.1; -; Genomic_DNA.
DR EMBL; AF482769; AAM18042.1; -; Genomic_DNA.
DR RefSeq; NP_001166125.1; NM_001172654.2. [Q8N6C8-2]
DR RefSeq; NP_006856.3; NM_006865.4. [Q8N6C8-1]
DR PDB; 3Q2C; X-ray; 2.50 A; A=24-120.
DR PDBsum; 3Q2C; -.
DR AlphaFoldDB; Q8N6C8; -.
DR SMR; Q8N6C8; -.
DR BioGRID; 116216; 12.
DR IntAct; Q8N6C8; 5.
DR GlyGen; Q8N6C8; 5 sites.
DR iPTMnet; Q8N6C8; -.
DR PhosphoSitePlus; Q8N6C8; -.
DR BioMuta; LILRA3; -.
DR DMDM; 92090611; -.
DR jPOST; Q8N6C8; -.
DR MassIVE; Q8N6C8; -.
DR PaxDb; Q8N6C8; -.
DR PeptideAtlas; Q8N6C8; -.
DR PRIDE; Q8N6C8; -.
DR ProteomicsDB; 72158; -. [Q8N6C8-1]
DR DNASU; 11026; -.
DR Ensembl; ENST00000612127.4; ENSP00000484119.1; ENSG00000278046.4. [Q8N6C8-1]
DR Ensembl; ENST00000615652.4; ENSP00000482971.1; ENSG00000273884.4. [Q8N6C8-1]
DR Ensembl; ENST00000617541.4; ENSP00000477708.1; ENSG00000275841.4. [Q8N6C8-2]
DR Ensembl; ENST00000619638.4; ENSP00000481818.1; ENSG00000275841.4. [Q8N6C8-1]
DR Ensembl; ENST00000620589.4; ENSP00000480386.1; ENSG00000276175.4. [Q8N6C8-1]
DR GeneID; 11026; -.
DR KEGG; hsa:11026; -.
DR UCSC; uc032ini.2; human. [Q8N6C8-1]
DR CTD; 11026; -.
DR DisGeNET; 11026; -.
DR GeneCards; LILRA3; -.
DR HGNC; HGNC:6604; LILRA3.
DR MIM; 604818; gene.
DR neXtProt; NX_Q8N6C8; -.
DR PharmGKB; PA30378; -.
DR InParanoid; Q8N6C8; -.
DR OrthoDB; 1000446at2759; -.
DR PhylomeDB; Q8N6C8; -.
DR TreeFam; TF336644; -.
DR PathwayCommons; Q8N6C8; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q8N6C8; -.
DR BioGRID-ORCS; 11026; 7 hits in 609 CRISPR screens.
DR GeneWiki; LILRA3; -.
DR GenomeRNAi; 11026; -.
DR Pharos; Q8N6C8; Tdark.
DR PRO; PR:Q8N6C8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8N6C8; protein.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0032396; F:inhibitory MHC class I receptor activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR016332; A1B_glyco/leuk_Ig-like_rcpt.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR Pfam; PF13895; Ig_2; 2.
DR PIRSF; PIRSF001979; Alpha_1B_glycoprot_prd; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Receptor; Reference proteome; Repeat; Secreted;
KW Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 24..439
FT /note="Leukocyte immunoglobulin-like receptor subfamily A
FT member 3"
FT /id="PRO_0000014818"
FT DOMAIN 27..108
FT /note="Ig-like C2-type 1"
FT DOMAIN 119..224
FT /note="Ig-like C2-type 2"
FT DOMAIN 226..315
FT /note="Ig-like C2-type 3"
FT DOMAIN 326..415
FT /note="Ig-like C2-type 4"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24085305"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24085305"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24085305"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24085305"
FT CARBOHYD 431
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24085305"
FT DISULFID 49..98
FT /evidence="ECO:0000269|PubMed:21559424,
FT ECO:0007744|PDB:3Q2C"
FT DISULFID 145..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 157..167
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 246..297
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 346..397
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1
FT /note="M -> MHRGLIHPQSSAVGGDAM (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_045886"
FT VAR_SEQ 158..221
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9079806"
FT /id="VSP_045887"
FT VARIANT 3
FT /note="P -> S (in dbSNP:rs11574606)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9278324, ECO:0000269|PubMed:9548455"
FT /id="VAR_016990"
FT VARIANT 107
FT /note="L -> R (in dbSNP:rs6509862)"
FT /evidence="ECO:0000269|PubMed:12750859"
FT /id="VAR_016991"
FT VARIANT 301
FT /note="Y -> H (in dbSNP:rs4473306)"
FT /evidence="ECO:0000269|PubMed:12750859"
FT /id="VAR_016992"
FT CONFLICT 105
FT /note="A -> V (in Ref. 5; AAH28208)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="S -> P (in Ref. 1; AAB68667)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="A -> T (in Ref. 6; AAM18037)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="S -> L (in Ref. 1; AAB68667)"
FT /evidence="ECO:0000305"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:3Q2C"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:3Q2C"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:3Q2C"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:3Q2C"
FT STRAND 58..65
FT /evidence="ECO:0007829|PDB:3Q2C"
FT HELIX 68..72
FT /evidence="ECO:0007829|PDB:3Q2C"
FT HELIX 75..79
FT /evidence="ECO:0007829|PDB:3Q2C"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:3Q2C"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:3Q2C"
FT STRAND 94..102
FT /evidence="ECO:0007829|PDB:3Q2C"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:3Q2C"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:3Q2C"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:3Q2C"
SQ SEQUENCE 439 AA; 47472 MW; 3932C6DA202ED5F5 CRC64;
MTPILTVLIC LGLSLDPRTH VQAGPLPKPT LWAEPGSVIT QGSPVTLRCQ GSLETQEYHL
YREKKTALWI TRIPQELVKK GQFPILSITW EHAGRYCCIY GSHTAGLSES SDPLELVVTG
AYSKPTLSAL PSPVVTSGGN VTIQCDSQVA FDGFILCKEG EDEHPQCLNS HSHARGSSRA
IFSVGPVSPS RRWSYRCYGY DSRAPYVWSL PSDLLGLLVP GVSKKPSLSV QPGPVVAPGE
KLTFQCGSDA GYDRFVLYKE WGRDFLQRPG RQPQAGLSQA NFTLGPVSRS YGGQYTCSGA
YNLSSEWSAP SDPLDILITG QIRARPFLSV RPGPTVASGE NVTLLCQSQG GMHTFLLTKE
GAADSPLRLK SKRQSHKYQA EFPMSPVTSA HAGTYRCYGS LSSNPYLLTH PSDPLELVVS
GAAETLSPPQ NKSDSKAGE
